Myasthenia gravis (MG) is an autoimmune disease that continues to be a significant cause of impaired vision despite advances in treatment and understanding of its pathophysiology. Weakness of extraocular muscle (EOM) occurs in about 90 percent of myasthenics and 15 percent of all myasthenics will only manifest ocular signs. Why EOM is affected more prominently than extremity muscle is not understood. Unlike extremity skeletal muscle, mammalian EOM contains multiterminal fibers, similar to the tonic and intermediate fibers of nonmammalian muscle, and expresses proteins that are usually found only in fetal muscle. There are 2 forms of the acetylcholine receptor (AChR); they are the fetal- and adult-types, which differ in one of the four distinct subunits. The fetal AChR contains a gamma subunit, while the adult channel contains an epsilon subunit in its place. Myasthenics have antibodies against both fetal and adult AChRs. We hypothesize that 1) EOM is preferentially affected by the autoimmune process because it contains unique epitopes, 2) one unique epitope is the fetal AChR, and 3) the fetal AChR is restricted to the multiterminal fibers of adult EOM because only these fibers express the gamma subunit. Since AChR expression is regulated primarily by pretranslational processes, detection of gamma subunit mRNA would be strong evidence of fetal AChR expression at the endplate. Using the polymerase chain reaction, we will study expression of the AChR subunit mRNAs in individual EOM fibers. We will then quantitate AChR subunit expression in single and multiterminal fibers to investigate possible differential mechanisms of transcriptional control of AChR. The long term goals are to study AChR subunit expression in human EOM and regulation of AChR expression in normal EOM.